Differential gene expression in acute lymphoblastic leukemia cells surviving allogeneic transplant

• Published in: Cancer Immunology and Immunotherapy Vol. 59; no. 11; pp. 1633 - 1644
• Main Authors: Shand, Jessica C, Jansson, Johan, Hsu, Yu-Chiao, Campbell, Andrew, Mullen, Craig A
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.11.2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Animals; Antigens; Antineoplastic agents; Biologi; Biological and medical sciences; Biology; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Biomedical Sciences; Biomedicinsk vetenskap; Blotting, Western; Bone marrow; bone marrow transplant; Bone Marrow Transplantation; Cancer Research; Cell and molecular biology; Cell- och molekylärbiologi; Drug Delivery Systems; Gene expression; Gene Expression Profiling; Graft Survival - physiology; Graft versus host disease; Graft vs Leukemia Effect - genetics; Graft-versus-leukemia; Hematologic and hematopoietic diseases; Hypotheses; Immunology; Immunotherapy; interferon-gamma; Interferon-gamma - genetics; Interferon-gamma - metabolism; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Minor Histocompatibility Antigens; NATURAL SCIENCES; NATURVETENSKAP; Oligonucleotide Array Sequence Analysis; Oncology; Original; Original Article; Pharmacology. Drug treatments; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Stem cell transplantation; Transplantation, Homologous; Tumor Cells, Cultured; Graft-versus-host disease; Bone marrow transplantation; Interferon-gamma; Graft-versus-leukemia; Leukemia; Graft versus leukemia reaction; Immunopathology; Graft versus host disease; Graft-versus-host diseases; Stem cell; Hematopoietic cell; Homograft; Malignant hemopathy; Transplantation; In vitro; Allogeneic system; Treatment; Surgery; Lymphoproliferative syndrome; Immunotherapy; Bone marrow; Graft; Acute lymphocytic leukemia; Cancer; Gamma interferon
• ISSN: 0340-7004; 1432-0851; 1432-0851
• DOI: 10.1007/s00262-010-0889-y

The effectiveness of allogeneic graft-versus-leukemia (GVL) activity in control of acute lymphoblastic leukemia is generally regarded as poor. One possible factor is dynamic adaptation of the leukemia cell to the allogeneic environment. This work tested the hypothesis that the pattern of gene expression in acute lymphoblastic leukemia cells in an allogeneic environment would differ from that in a non-allogeneic environment. Expression microarray studies were performed in murine B lineage acute lymphoblastic leukemia cells recovered from mice that had undergone allogeneic MHC-matched but minor histocompatibility antigen mismatched transplants. A limited number of genes were found to be differentially expressed in ALL cells surviving in the allogeneic environment. Functional analysis demonstrated that genes related to immune processes, antigen presentation, ubiquitination and GTPase function were significantly enriched. Several genes with known immune activities potentially relevant to leukemia survival (Ly6a/Sca-1, TRAIL and H2-T23) were examined in independent validation experiments. Increased expression in vivo in allogeneic hosts was observed, and could be mimicked in vitro with soluble supernatants of mixed lymphocyte reactions or interferon-gamma. The changes in gene expression were reversible when the leukemia cells were removed from the allogeneic environment. These findings suggest that acute lymphoblastic leukemia cells respond to cytokines present after allogeneic transplantation and that these changes may reduce the effectiveness of GVL activity.